371P - Efficacy of metronomic capecitabine plus aromatase inhibitor as initial therapy in patients with hormone receptor-positive, HER2-negative metastatic breast cancer: The phase III MECCA trial

Background

Metronomic chemotherapy, characterized by the administration of low-dose chemotherapy agents at a high frequency, has demonstrated clinical efficacy in breast cancer with milder toxicity compared to conventional chemotherapy. Various anti-tumoral mechanisms, including angiogenesis inhibition and modification of the tumor microenvironment, have been shown to be associated with metronomic chemotherapy. Retrospective studies and phase II clinical trials showed promising activity of the metronomic chemotherapy and endocrine therapy combination strategy in hormone receptor-positive (HR+), human epidermal growth factor receptor2 (HER2)-negative metastatic breast cancer, with good tolerance. This phase 3 study aimed to assess the efficacy and safety of the metronomic capecitabine plus aromatase inhibitor (AI) regimen as initial therapy in this patient population.

Methods

In this multicenter, randomized study, 263 women with HR+, HER2-negative metastatic breast cancer, who had no prior systemic therapy in the metastatic setting, were 1:1 assigned to receive either metronomic capecitabine (500mg, three times daily) plus an AI or an AI alone. The primary endpoint was progression-free survival (PFS) per investigators' assessment. The secondary endpoints included overall survival (OS), objective response rate, disease control rate (defined as disease controlled for ≥24 weeks), and safety.

Results

A total of 254 patients were subjected to efficacy analysis. The metronomic capecitabine plus AI arm exhibited a median PFS of 20.9 months compared to 11.9 months in the AI arm (hazard ratio 0.58; 95% CI, 0.44 to 0.77; p=0.0001). Median OS was not reached in the combination arm and was 45.1 months in the AI arm (hazard ratio 0.56; 95% CI, 0.35 to 0.89; p=0.0139). The most common adverse events were palmar-plantar erythrodysesthesia and peripheral neuropathy; grade 3 or 4 events occurred in 15.1% of the patients receiving combination treatment.

Conclusions

The MECCA trial demonstrated a significant improvement in PFS and OS with first-line metronomic capecitabine plus AI compared to AI alone in patients with HR+/HER2-negative metastatic breast cancer.

Clinical trial identification

NCT02767661.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Sun Yat-sen University.

Disclosure

All authors have declared no conflicts of interest.